Document Detail


[Mechanisms for linking high salt intake to vascular tone: role of Na(+) pump and Na(+)/Ca²(+) exchanger coupling].
MedLine Citation:
PMID:  21048395     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Excessive salt intake is a major risk factor for hypertension. However, the underlying molecular relationship between salt and hypertension is not fully understood. Recently discovered cardiotonic steroids, such as endogenous ouabain and other steroids, have been proposed as candidate intermediaries. Plasma cardiotonic steroids are significantly elevated in patients with essential hypertension and in salt-dependent hypertensive animals. Generally, it is believed that cardiotonic steroids inhibit Na(+) pump activity and lead to an increase in the cytosolic Na(+) concentration. Cellular Na(+) accumulation raises the cytosolic Ca²(+) concentration through the involvement of Na(+)/Ca²(+) exchanger type 1 (NCX1). In isolated arteries from α2 Na(+) pump knockout mice (α2(+/-)), myogenic tone is increased, and NCX inhibitor normalizes the elevated myogenic tone in α2(+/-) arteries. The NCX inhibitor lowers arterial blood pressure in salt-dependent hypertensive rats but not in other types of hypertensive rats or in normotensive rats. Furthermore, smooth muscle-specific NCX1 transgenic mice are hypersensitive to salt, whereas mice with smooth muscle-specific knockout of NCX1 (NCX1(SM-/-)) have low salt sensitivity. These results suggest that functional coupling between the vascular α2 Na(+) pump and NCX1 is a critical molecular mechanism for salt-induced blood pressure elevation.
Authors:
Satomi Kita; Takahiro Iwamoto
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Publication Detail:
Type:  English Abstract; Journal Article    
Journal Detail:
Title:  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan     Volume:  130     ISSN:  0031-6903     ISO Abbreviation:  Yakugaku Zasshi     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413613     Medline TA:  Yakugaku Zasshi     Country:  Japan    
Other Details:
Languages:  jpn     Pagination:  1399-405     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Faculty of Medicine, Fukuoka University, Japan. Satokita@fukuoka-u.ac.jp
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